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https://www.readbyqxmd.com/read/28922811/a-programme-to-create-short-course-chemotherapy-for-pulmonary-mycobacterium-avium-disease-based-on-pharmacokinetics-pharmacodynamics-and-mathematical-forecasting
#1
Devyani Deshpande, Shashikant Srivastava, Tawanda Gumbo
Objectives: Pulmonary Mycobacterium avium complex (MAC) prevalence is on the rise worldwide. The average therapy duration is 1.5 years, which is associated with poor cure rates. Our objective was to develop a programme to design a combination therapy regimen for pulmonary MAC to be administered for 6 months or less with efficacy in > 90% of patients. Methods: We performed a literature search for the following MeSH headings 'Mycobacterium avium' AND 'pharmacokinetics/pharmacodynamics' in PubMed up to 2016...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922810/a-shock-and-awe-thioridazine-and-moxifloxacin-combination-based-regimen-for-pulmonary-mycobacterium-avium-intracellulare-complex-disease
#2
Shashikant Srivastava, Devyani Deshpande, Carleton M Sherman, Tawanda Gumbo
Objectives: To develop a thioridazine/moxifloxacin-based combination regimen for treatment of pulmonary infection due to Mycobacterium avium-intracellulare complex (MAC) that kills bacteria faster than the standard treatment regimen. Methods: Monocytes were infected with MAC and inoculated into the hollow-fibre system model for pulmonary MAC disease (HFS-MAC). We co-administered ethambutol plus azithromycin daily for 28 days, to achieve the same human concentration-time profiles that result from standard doses, in three HFS-MAC systems...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922809/a-novel-ceftazidime-avibactam-rifabutin-tedizolid-and-moxifloxacin-cartm-regimen-for-pulmonary-mycobacterium-avium-disease
#3
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To compare the efficacy of ceftazidime/avibactam plus tedizolid-based combination regimens with the standard therapy of azithromycin, ethambutol and rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Methods: We mimicked the human pulmonary concentration-time profiles of ceftazidime/avibactam and tedizolid in combination, ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM), and the standard regimen and examined microbial kill in triplicate hollow-fibre system model of intracellular pulmonary MAC (HFS-MAC) units...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922808/the-discovery-of-ceftazidime-avibactam-as-an-anti-mycobacterium-avium-agent
#4
Devyani Deshpande, Shashikant Srivastava, Moti L Chapagain, Pooi S Lee, Kayle N Cirrincione, Jotam G Pasipanodya, Tawanda Gumbo
Objectives: To determine if ceftaroline and ceftazidime combined with avibactam are efficacious against pulmonary Mycobacterium avium complex (MAC) disease. Methods: First, we performed a concentration-effect study of ceftaroline and ceftaroline/avibactam against extracellular MAC in test tubes. Given the difficulty of obtaining avibactam at the time of experimentation, we used a single concentration of commercial ceftazidime/avibactam, and two sets of non-treated controls, one with ceftazidime/avibactam and the other without...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922807/tedizolid-is-highly-bactericidal-in-the-treatment-of-pulmonary-mycobacterium-avium-complex-disease
#5
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To determine if tedizolid is effective for pulmonary Mycobacterium avium complex (MAC) disease, and to use pharmacokinetics/pharmacodynamics to design optimal doses. Methods: We performed an exposure-response experiment in the hollow-fibre system model of intracellular MAC (HFS-MAC). We mimicked the tedizolid concentration-time profiles achieved in the lungs of patients treated once daily for 28 days. The HFS-MAC was sampled at intervals to determine the tedizolid pharmacokinetics and MAC intracellular burden...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922806/linezolid-as-treatment-for-pulmonary-mycobacterium-avium-disease
#6
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Tawanda Gumbo
Objectives: To identify the pharmacokinetic/pharmacodynamic parameters and exposures of linezolid in the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Methods: Human-derived monocytes infected with MAC were inoculated into hollow-fibre systems for dose-effect and dose-scheduling studies. We mimicked linezolid concentration-time profiles achieved in adult human lungs treated for 28 days. Sampling to confirm that the intended linezolid pharmacokinetics had been achieved, and for enumeration of MAC colony-forming units, was performed based on repetitive sampling from each system over the 28 days...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922805/failure-of-the-azithromycin-and-ethambutol-combination-regimen-in-the-hollow-fibre-system-model-of-pulmonary-mycobacterium-avium-infection-is-due-to-acquired-resistance
#7
Shashikant Srivastava, Devyani Deshpande, Tawanda Gumbo
Objectives: To investigate the performance of the two backbone drugs in the standard combination therapy regimen in the hollow-fibre system (HFS) model of pulmonary Mycobacterium avium complex (MAC) infection. Methods: Six HFS were inoculated with human-derived monocytes infected with MAC, and treated with 15 mg/kg of ethambutol and 500 mg of azithromycin daily for 28 days to recapitulate the concentration-time profiles seen in the lungs of humans treated with these drugs and doses...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922791/targeting-hypoxia-to-improve-non-small-cell-lung-cancer-outcome
#8
Ahmed Salem, Marie-Claude Asselin, Bart Reymen, Alan Jackson, Philippe Lambin, Catharine M L West, James P B O'Connor, Corinne Faivre-Finn
Oxygen deprivation (hypoxia) in non-small cell lung cancer (NSCLC) is an important factor in treatment resistance and poor survival. Hypoxia is an attractive therapeutic target, particularly in the context of radiotherapy, which is delivered to more than half of NSCLC patients. However, NSCLC hypoxia-targeted therapy trials have not yet translated into patient benefit. Recently, early termination of promising evofosfamide and tarloxotinib bromide studies due to futility highlighted the need for a paradigm shift in our approach to avoid disappointments in future trials...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922734/persistent-antidepressant-effect-of-low-dose-ketamine-and-activation-in-the-supplementary-motor-area-and-anterior-cingulate-cortex-in-treatment-resistant-depression-a-randomized-control-study
#9
Mu-Hong Chen, Cheng-Ta Li, Wei-Chen Lin, Chen-Jee Hong, Pei-Chi Tu, Ya-Mei Bai, Chih-Ming Cheng, Tung-Ping Su
A single low-dose ketamine infusion exhibited a rapid antidepressant effect within 1h. Despite its short biological half-life (approximately 3h), the antidepressant effect of ketamine has been demonstrated to persist for several days. However, changes in brain function responsible for the persistent antidepressant effect of a single low-dose ketamine infusion remain unclear METHODS: Twenty-four patients with treatment-resistant depression (TRD) were randomized into three groups according to the treatment received: 0...
September 9, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28922729/lithium-induced-oxidative-damage-and-inflammation-in-the-rat-s-heart-protective-effect-of-grape-seed-and-skin-extract
#10
Ali Mezni, Hanène Aoua, Olfa Khazri, Ferid Limam, Ezzeddine Aouani
Lithium (Li) is a relevant mood stabilizer metal for the treatment of bipolar disorder (BD), as it protects from both depression and mania and reduces the risk of suicide. However, Lihas some clinical concerns as a narrow therapeutic index requiring routine monitoring of the serum level. The present study was designed to analyze the cardio-toxic side effect of Li and the ability of grape seed and skin extract (GSSE) to protect the heart against such toxicity. After 30days of exposure to Li (0, 2, 5 and 100mg/kg bw) and prevention with GSSE (4000mg/kg bw), rats were killed by decapitation and their heart processed for Li-induced oxidative stress...
September 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922724/oyster-ostrea-plicatula-gmelin-polysaccharides-intervention-ameliorates-cyclophosphamide-induced-genotoxicity-and-hepatotoxicity-in-mice-via-the-nrf2-are-pathway
#11
Shuting Lin, Gengxin Hao, Min Long, Fei Lai, Qingqin Li, Yongmei Xiong, Yan Tian, Dong Lai
In this study, we explored the protective effects of oyster (Ostrea plicatula Gmelin) polysaccharides (OPS) against genotoxicity and liver injury induced by cyclophosphamide (CP) in BALB/c mice. OPS was administered to mice at doses of 100 and 200mg/kg for 7 consecutive days, then 50mg/kg CP was injected via abdomen. Then mice were sacrificed and samples were collected. Bone marrow micronuclei (MN) and polychromatic erythrocytes (PCE): normochromatic erythrocytes (NCE) ratio were calculated to evaluate CP induced genetic toxicity...
September 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922723/protective-effects-of-mirtazapine-and-chrysin-on-experimentally-induced-testicular-damage-in-rats
#12
Alaa E El-Sisi, Magda E El-Sayad, Nermine M Abdelsalam
Mirtazapine is an antidepressant with prominent antioxidant effects. Chrysin, a natural flavone, exhibits multiple pharmacological actions. This study was designed to investigate the potential protective effects of chrysin and mirtazapine against nitrofurazone-induced testicular damage in rats. Possible underlying mechanisms such as oxidative stress, inflammation and apoptosis were also investigated. Testicular damage was induced by oral administration of nitrofurazone (50mg/kg/day) for two weeks. Chrysin (25 and 50mg/kg/day, p...
September 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922714/atmospheric-levels-and-cytotoxicity-of-polycyclic-aromatic-hydrocarbons-and-oxygenated-pahs-in-pm2-5-in-the-beijing-tianjin-hebei-region
#13
Xinyi Niu, Steven Sai Hang Ho, Kin Fai Ho, Yu Huang, Jian Sun, Qiyuan Wang, Yaqing Zhou, Zhuzi Zhao, Junji Cao
The chemical composition of PM2.5 and cellular effects from exposure to fine aerosol extracts were studied for samples collected in Beijing, Tianjin, Shijiazhuang, and Hengshui, China in winter 2015. Effects of priority polycyclic aromatic hydrocarbons (PAHs) and their oxygenated derivatives (OPAHs) in PM2.5 on cell cultures were a major focus of the study. Total quantified PAHs and OPAHs at Shijiazhuang and Hengshui were higher than at Beijing and Tianjin, and benz(a)anthracene, chrysene and 1,8-naphthalic anhydride were the most abundant species...
September 12, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28922713/peppermint-essential-oil-alleviates-hyperglycemia-caused-by-streptozotocin-nicotinamide-induced-type-2-diabetes-in-rats
#14
Suhair A Abdellatief, Rasha R Beheiry, Shefaa A M El-Mandrawy
The prevalence of diabetes mellitus is steadily growing throughout the world. Traditional medicine has an excellent potential in the treatment of diabetes mellitus. The present study was undertaken to evaluate the potential antidiabetic effect of peppermint essential oil (PEO) on streptozotocin (STZ) and nicotinamide induced diabetic rats. Diabetes was induced in rats fasting overnight by the intraperitoneal administration of nicotinamide followed by a single dose of STZ. After 72h, two groups of diabetic rats were treated with different doses of PEO (40 and 80mg/kg BW) respectively and one group was treated with the standard hypoglycemic agent glibenclamide...
September 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922669/a-critical-commentary-on-the-2017-agnp-consensus-guidelines-for-therapeutic-drug-monitoring-in-neuropsychopharmacology
#15
Jose de Leon
In 2004, 2011, and 2017, the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP), a group of German-speaking psychiatric researchers and psychiatrists, published successive versions of therapeutic drug monitoring (TDM) expert group consensus guidelines. The 2017 version has as a major strength its encyclopedic nature, including 1358 references. The guideline has 3 major sections: 1) theoretical aspects of TDM, 2) drug concentration levels in blood to guide neuropsychopharmacotherapy, and 3) practical aspects of TDM in psychiatry and neurology...
September 18, 2017: Pharmacopsychiatry
https://www.readbyqxmd.com/read/28922612/analysis-of-levodopa-content-in-commercial-mucuna-pruriens-products-using-high-performance-liquid-chromatography-with-fluorescence-detection
#16
Amala Soumyanath, Tanya Denne, Amie Hiller, Shaila Ramachandran, Lynne Shinto
OBJECTIVES: Mucuna pruriens (MP) seeds contain levodopa (up to 2% by weight) and have been used in traditional Indian medicine to treat an illness named "Kampavata," now understood to be Parkinson's disease (PD). Studies have shown MP to be beneficial, and even superior, to levodopa alone in treating PD symptoms. Commercial products containing MP are readily available from online and retail sources to patients and physicians. Products often contain extracts of MP seeds, with significantly higher levodopa content than the seeds...
September 18, 2017: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
https://www.readbyqxmd.com/read/28922594/dose-dependent-response-to-3-nitrobenzanthrone-exposure-in-human-urothelial-cancer-cells
#17
Mario Pink, Nisha Verma, Anna Zerries, Simone Schmitz-Spanke
A product of incomplete combustion of diesel fuel, 3-nitrobenzanthrone (3-NBA), has been classified as a cancer-causing substance. It first gained attention as a potential urinary bladder carcinogen due to the presence of its metabolite in urine and formation of DNA adducts. The aim of the present study was to characterise the dose-response relationship of 3-NBA in human urothelial cancer cell line (RT4) exposed to concentrations ranging from 0.0003 µM (environmentally relevant) to 80 µM by utilising toxicological and metabolomic approaches...
September 18, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28922591/baseline-characteristics-and-early-response-at-week-1-predict-treatment-outcome-in-adolescents-with-bipolar-manic-or-mixed-episode-treated-with-olanzapine-results-from-a-3-week-randomized-placebo-controlled-trial
#18
Le Xiao, Stephen J Ganocy, Robert L Findling, Kiki Chang, Melissa P DelBello, John M Kane, Mauricio Tohen, Yu-Tao Xiang, Christoph U Correll
BACKGROUND: Early predictors of response and remission in pediatric mania are lacking, requiring further study. METHODS: This was a post hoc analysis of a 3-week, randomized, placebo-controlled trial of olanzapine conducted between November 2002 and May 2005 in 161 adolescents aged 13-17 years who were diagnosed with a DSM-IV acute manic or mixed episode of bipolar I disorder. Data from the olanzapine arm were analyzed to investigate the predictive power of early response or early nonresponse (≥25% or < 25% reduction in Young Mania Rating Scale [YMRS] score, respectively) at week 1 for ultimate response or nonresponse (≥ 50% or < 50% reduction in YMRS score, respectively) and for remission (YMRS total score ≤ 12 [standard definition] or ≤ 8 [stringent definition]) at week 3...
September 5, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28922590/efficacy-and-safety-of-the-%C3%AE-7-nicotinic-acetylcholine-receptor-agonist-abt-126-in-the-treatment-of-cognitive-impairment-associated-with-schizophrenia-results-from-a-phase-2b-randomized-controlled-study-in-smokers
#19
George M Haig, Deli Wang, Jun Zhao, Ahmed A Othman, Earle E Bain
OBJECTIVE: To evaluate the efficacy and safety of the α₇-nicotinic receptor agonist ABT-126 for treatment of cognitive impairment in stable subjects with schizophrenia who smoke. METHODS: A 12-week double-blind, placebo-controlled, parallel-group study was conducted from August 2012 to March 2014. Subjects with a diagnosis of schizophrenia based on DSM-IV-TR criteria (confirmed by the Mini-International Neuropsychiatric Interview version 6.0.0) were randomized 1:1:1 to ABT-126 25 mg, ABT-126 75 mg, or placebo once daily while maintained on their background antipsychotic medication...
September 12, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28922582/relationship-between-optimum-mini-doses-of-glucagon-and-insulin-levels-when-treating-mild-hypoglycaemia-in-patients-with-type-1-diabetes-a-simulation-study
#20
Ajenthen Ranjan, Sabrina L Wendt, Signe Schmidt, Sten Madsbad, Jens J Holst, Henrik Madsen, Carsten B Knudsen, John B Jørgensen, Kirsten Nørgaard
Hypoglycaemia remains the main limiting factor in type 1 diabetes management. We developed an insulin-dependent glucagon dosing regimen for treatment of mild hypoglycaemia based on simulations. A validated glucose-insulin-glucagon model was used to describe seven virtual patients with insulin pump-treated type 1 diabetes. In each simulation, one of ten different and individualised subcutaneous insulin boluses was administered to decrease plasma glucose (PG) from 7.0 to ≤3.9 mmol/l. Insulin levels were estimated as ratio of actual to baseline serum insulin concentration (se/ba-insulin), insulin on board (IOB) or percentage of IOB to total daily insulin dose (IOB/TDD)...
September 18, 2017: Basic & Clinical Pharmacology & Toxicology
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